Cardiomyopathy associated with the administration of chemotherapeutic antibiotics will be investigated at the cellular and molecular levels of biological complexity. Myocardial cells in culture will be used as a model system in the investigation of the effect of the antibiotics on: the morphology, rate, and strength of the spontaneous rhythmic contractions, the membrane characteristics, and the enzymes involved in the contractile machinery, and in the associated energy production. Also, the extent of nucleotide misincorporation frequencies (error induction and correction in DNA and RNA) will be studied in dividing and non-dividing rat heart cells in culture. Extracts from whole hearts will be used for the preparation of nucleases and polymerases necessary for the reconstitution of the editing system in vitro. Papillary muscles isolated from hearts of rabbits and rats will be the model system for the study of the effect of the chemotherapeutic agents on the mechanical characteristics of the myocardium. The information sought for in this study should be of importance in determining the mechanism of action of the antibiotics and could lead to an understanding of the severe cardiotoxic side effects. BIBLIOGRAPHIC REFERENCES: J.K. Hardman, H. Berger, and M.F. Goodman, Tryptophan Operon Read-Through, J. Biol. Chem. 250, 4624 (1975). M.F. Goodman, Y.S. Chang, and N.R. Bachur, Response of mutant and wild-type DNA polymerases to Antracycline derivatives, Fed. Proc. 34, 493 (1975).